Lithium Fluoride1

LiF

[7789-24-4]  · (MW 25.94)

(mild base;2 can replace other halogens with fluorine;3 desilylation reagent for forming reactive azomethine ylides;4 stereoselective oxidative desulfurization when used with MeI and Li2CO35)

Physical Data: mp 848 °C; bp 1681 °C; d 2.639 g cm-3.

Solubility: sol 0.27 g per 100 g water at 18 °C.

Form Supplied in: white solid; fused pieces and random crystals; widely available.

Handling, Storage, and Precautions: avoid breathing dust and contact with eyes, skin, or clothing.

Fluorination Agent.

Lithium fluoride can be used to exchange other halogens with fluorine. The reactivity of lithium fluoride is weaker than Potassium Fluoride and it cannot displace less reactive halogens, such as aryl chlorides or bromides. Glycerol chlorohydrin can be converted to the corresponding fluorohydrin in moderate yield (eq 1).3 Treatment of dichloroboranes with lithium fluoride in ether gives the corresponding difluoroboranes in good yield (eq 2).6 Lithium fluoride can also exchange with chlorine atoms7 and trifluoromethanesulfonyloxy groups8 on silicones to give the corresponding fluorinated silane derivatives (eqs 3 and 4).

Desilylation Agent.

Lithium fluoride has been found to be the most effective desilylating reagent for N-[(trimethylsilyl)methyl]amino ethers in the formation of azomethine ylides which can undergo 1,3-dipolar cycloaddition reactions with reactive dipolarophiles in high yield.4 This is a very useful method for the preparation of pyrrolidines. A mixture of N-benzyl-N-methoxymethyl-N-(trimethylsilyl)methylamine and N-phenylmaleimide with LiF in anhydrous acetonitrile was sonicated for 3 h to give the cycloadduct in 72-75% yield (eq 5).9 The cycloaddition proceeded with complete stereospecificity with dimethyl maleate and fumarate, giving rise to cis (eq 6) and trans (eq 7) cycloadducts, respectively. This cycloaddition did not take place with methyl propiolate; instead, the reaction gave the conjugate addition product (eq 8).

Desulfurization.

A mixture of lithium fluoride, Iodomethane and Lithium Carbonate is an effective reagent for the desulfurization of allylic dithiocarbamates.5 All-trans-2,4,6,8-decatetraene was prepared in 75-80% yield (eq 9).10 Terminal silyl derivatives can undergo this oxidative desulfurization regioselectively to form the terminal double bond, leaving the existing double bonds intact (eq 10).11

Related Reagents.

Potassium Fluoride; Potassium Fluoride-Alumina; Potassium Fluoride-Celite.


1. Hudlický, M. Chemistry of Organic Fluorine Compounds, 2nd ed.; Horwood: New York, 1992; pp 25-131.
2. Kirk, D. N.; Patel, D. K.; Petrow, V. JCS 1956, 627.
3. Oláh, G.; Pavláth, A. Acta Chim. Acad. Sci. Hung. 1953, 3, 431.
4. (a) Padwa, A.; Dent, W. JOC 1987, 52, 235. (b) Pandey, G.; Lakshmaiah, G. TL 1993, 34, 4861.
5. Hayashi, T.; Sakurai, A.; Oishi, T. CL 1977, 1483.
6. Kaufmann, D. CB 1987, 120, 901.
7. Hensen, K.; Pickel, P. LA 1980, 223.
8. Hengge, E. F.; Hassler, K.; Schrank, F. HC 1990, 1, 455.
9. Padwa, A.; Dent, W. OS 1988, 67, 133; OSC 1994, 8, 231.
10. Hayashi, T.; Hori, I.; Oishi, T. JACS 1983, 105, 2909.
11. Hayashi, T.; Yanagida, M.; Matsuda, Y.; Oishi, T. TL 1983, 24, 2665.

Ying Song

University of Delaware, Newark, DE, USA

Hui-Yin Li

The Du Pont Merck Pharmaceutical Company, Wilmington, DE, USA



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